This application is in response to the RFA [unreadable]Great Lakes Human Health Effects Research Program (RFA-TS-07-001)[unreadable], and the goal of the proposed work is to evaluate the risk of disease occurrence that is associated with long-term consumption of contaminated Great Lakes fish. To achieve this goal, we will conduct a mailed follow-up health survey in a large established and well characterized cohort of adults enrolled in the New York State Anglers Cohort Study (NYSACS). Study participants are 18,963 middle-aged women and men who are New York State fishing license holders and who reside in 16 New York counties that border Lakes Ontario and Erie in New York State. An important feature of the NYSACS is the detailed and precise assessment of Great Lakes fishing habits and fish consumption at baseline in 1991, and then again during an initial follow-up survey that was conducted in 1997. Questionnaire items focused on information pertaining to the frequency (in years) of harvesting and eating fish from waters in the Great Lakes Basin, the specific species and size of fish harvested and consumed, and how fish was prepared and cooked, both in the 12 months preceding completion of the questionnaire and historically across the period 1955-1991. Research activities to date have focused on developmental and reproductive health consequences associated with Great Lakes fish consumption. We propose herein to extend and expand on the existing follow-up in the NYSACS in order to ascertain the occurrence of several fatal and nonfatal health endpoints and to relate these outcomes with reported Great Lakes fish consumption, recent and long-term each. Study strengths include the experience of the research team, the large characterized population sample of anglers who already have demonstrated a willingness to complete and return mailed follow-up health surveys, the detailed exposure assessment on contaminated fish consumption, and the relative cost- effectiveness of the proposed work which essentially is to continue and expand follow-up in the already established NYSACS. Findings from this proposed study could inform on improving existing public health recommendations on contaminated Great Lakes fish consumption. To address a major objective in the CDC/ATSDR RFA [unreadable]Great Lakes Human Health Effects Research Program[unreadable] (RFA-TS-07-001), we will prospectively examine the association between long-term Lake Ontario fish consumption and chronic disease risk in an established large cohort of anglers and their spouses.